OverweightNCT03860558
Impact of Metabolic Health on Sperm Epigenetic Marks in Humans
A study testing Lifestyle Intervention in people with Overweight and Type 2 Diabetes Mellitus, run by Joslin Diabetes Center at 1 site in United States.
Trial summary
This study is designed to evaluate whether epigenetic markers in overweight men with type 1 diabetes (T1D) or type 2 diabetes (T2D) can be improved with a 3 month lifestyle intervention or program focused in glycemic intervention. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Overweight, Type 2 Diabetes Mellitus, Type 1 Diabetes Mellitus
- What is being tested?
- Lifestyle Intervention
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2018to 1 Jul 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male, age 18-65 years
- Willing and able to provide informed consent and follow all study procedures, including providing sperm specimens 3 months apart.
- Type 1 or type 2 diabetes diagnosis confirmed by an endocrinologist (for participants in the diabetes groups)
- HbA1c > 7% (for participants in the diabetes groups)
- Overweight (BMI > 25 kg/m2) (for all groups, to ensure groups are similar)
Who cannot join
- Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
- Hepatic disease, including serum alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;
- Severe diabetic retinopathy;
- Congestive heart failure, New York Heart Association (NYHA) class II, III or IV;
- History of myocardial infarction, unstable angina or revascularization within the past 6 months;
- Active genitourinary infection;
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- Testicular volume <12 mL (assessed using Prader orchidometer);
- Hypogonadism, defined as total testosterone <250 ng/dl;
- Hyperprolactinemia, defined as prolactin >18 ng/ml;
- Hyperestrogenism, defined as estradiol >42 pg/ml;
- Cryptorchidism;
- Cigarette smoking;
- Active alcohol abuse or substance abuse;
- Cancer (except localized non-melanoma skin cancers) or use of chemotherapy agents within 5 years;
- Use of nitrates or guanylate cyclase stimulators;
- Use of steroid hormones (including testosterone), other than inhalers for reactive airway disease
Trial locations and contacts
1 site in 1 country.
About this study
This study is designed to evaluate whether epigenetic markers in overweight men with type 1 diabetes (T1D) or type 2 diabetes (T2D) can be improved with a 3 month lifestyle intervention or program focused in glycemic intervention.
Read the detailed description
Parental history of diabetes confers substantial individual risk for development of obesity and diabetes. Obesity risk can be transmitted across generations, from parents or grandparents to children. Genomic variation explains only a portion of this risk. Epigenetic modulation through DNA methylation, histone modification, or by noncoding RNAs, provide mechanisms to regulate gene activity independent of DNA sequence by determining which genes are turned on or off in response to environment or disease. Epigenetic changes can be stable over the lifespan providing a mechanism through which environmental exposures may impart long-term effects on gene expression and phenotypic outcome.
The maternal intrauterine environment is now well recognized to modify obesity and T2D disease risk of offspring. Fetuses carried by women who are obese, have diabetes, or suffer from suboptimal nutrition are at increased risk of insulin resistance, obesity, T2D, and cardiovascular disease risk as adults. Studies in rodents also show that the health, metabolism, and prior environmental exposures of the male can also influence health of his offspring. Existing data provide powerful support for the hypothesis that current glucose levels and overall metabolic health of males can alter epigenetic marks in sperm and suggest a novel modifiable mechanism of transmission. However, much less is known about how human sperm epigenetic patterns change with nutritional and metabolic health, and whether these may ultimately impart differences in health of future generations. Thus, we are studying the impact of both type 1 and type 2 diabetes, and elevations in glucose common to both conditions, on human reproductive health and the sperm epigenome.
- Being tested
- Lifestyle Intervention, No Intervention
- Medical subject headings
- Overweight, Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lifestyle InterventionOther
Participants will undergo a 12-week multidisciplinary program for weight control and intensive diabetes management. The program includes adjustments to diabetes medications to enhance weight reduction and improve glycemia, dietary modification, and activity instructions.
No InterventionOther
Participants will not undergo an intervention.
| Study group | Role | What they receive |
|---|---|---|
| Lifestyle Intervention | Experimental | 20 overweight men with T1D or T2D will undergo an intensive 3 month lifestyle intervention program aimed at improving metabolic health, glycemic control, and body weight. Receives: Other: Lifestyle Intervention |
| No-Intervention Controls | Active comparator | 10 overweight men with T1D or T2D will be assessed at baseline and at 3 months. They will not participate in a lifestyle intervention. Receives: Other: No Intervention |
| Healthy Controls | Active comparator | 10 healthy men will be assessed at baseline and at 3 months. They will not participate in a lifestyle intervention. Receives: Other: No Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spermatozoa concentration
Sperm will be assessed for concentration, reported as total yield (millions per ml)
Measured: 1 year
Secondary outcomes (2)
Sperm DNA methylation, reported as genomic location of regions with methylation altered in response to intervention
We will utilize purified DNA (1.5 μg), sheared by sonication to obtain 200-700 bp fragments for subsequent library preparation for methylation-dependent immunoprecipitation and sequencing. Differentially methylated regions (DMR) are identified using methylated DNA immunoprecipitation coupled with next-generation sequencing (MEDIPS). DNA methylation is assessed using sliding windows (500 bp size, 200 bp shift). Regions with read ratios >1.5 or <0.67 and binomial p<0.0001 in independent biologically replicated comparisons are designated as DMR.
Measured: 1 year
RNA Sequencing
RNA will be isolated from sperm samples and subjected to RNA sequencing to analyze the content of both of large messenger ribonucleic acid (mRNA)/noncoding RNA and small RNAs. Data will be analyzed to identify those species altered in response to intervention.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2019
- Study start1 May 2018
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for OverweightStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Joslin Diabetes Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03860558
- Sponsor's protocol ID
- 2015-40
- Status last verified
- Feb 2026
- First submitted
- 11 Oct 2018
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sales VM, Ferguson-Smith AC, Patti ME. Epigenetic Mechanisms of Transmission of Metabolic Disease across Generations. Cell Metab. 2017 Mar 7;25(3):559-571. doi: 10.1016/j.cmet.2017.02.016.
PubMed 28273478Su L, Dreyfuss JM, Ferraz Bannitz R, Wolfs D, Hansbury G, Richardson L, Charmant C, Patel J, Ginsburg ES, Racowsky C, Fore R, Efthymiou V, Desmond J, Goldfine A, Ferguson-Smith A, Pan H, Hivert MF, Isganaitis E, Patti ME. Type 2 diabetes impacts DNA methylation in human sperm. Clin Epigenetics. 2025 Mar 20;17(1):49. doi: 10.1186/s13148-025-01853-9.
PubMed 40108650
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Metabolic Health on Sperm Epigenetic Marks in Humans
- ClinicalTrials.gov ID
- NCT03860558
- Acronym / sponsor ID
- 2015-40
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Joslin Diabetes CenterUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Jul 2026 (estimated)
- First posted
- 4 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate whether epigenetic markers in overweight men with type 1 diabetes (T1D) or type 2 diabetes (T2D) can be improved with a 3 month lifestyle intervention or program focused in glycemic intervention.
Detailed description
Parental history of diabetes confers substantial individual risk for development of obesity and diabetes. Obesity risk can be transmitted across generations, from parents or grandparents to children. Genomic variation explains only a portion of this risk. Epigenetic modulation through DNA methylation, histone modification, or by noncoding RNAs, provide mechanisms to regulate gene activity independent of DNA sequence by determining which genes are turned on or off in response to environment or disease. Epigenetic changes can be stable over the lifespan providing a mechanism through which environmental exposures may impart long-term effects on gene expression and phenotypic outcome.
The maternal intrauterine environment is now well recognized to modify obesity and T2D disease risk of offspring. Fetuses carried by women who are obese, have diabetes, or suffer from suboptimal nutrition are at increased risk of insulin resistance, obesity, T2D, and cardiovascular disease risk as adults. Studies in rodents also show that the health, metabolism, and prior environmental exposures of the male can also influence health of his offspring. Existing data provide powerful support for the hypothesis that current glucose levels and overall metabolic health of males can alter epigenetic marks in sperm and suggest a novel modifiable mechanism of transmission. However, much less is known about how human sperm epigenetic patterns change with nutritional and metabolic health, and whether these may ultimately impart differences in health of future generations. Thus, we are studying the impact of both type 1 and type 2 diabetes, and elevations in glucose common to both conditions, on human reproductive health and the sperm epigenome.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lifestyle Intervention | Experimental | Other: Lifestyle Intervention20 overweight men with T1D or T2D will undergo an intensive 3 month lifestyle intervention program aimed at improving metabolic health, glycemic control, and body weight. |
| No-Intervention Controls | Active comparator | Other: No Intervention10 overweight men with T1D or T2D will be assessed at baseline and at 3 months. They will not participate in a lifestyle intervention. |
| Healthy Controls | Active comparator | Other: No Intervention10 healthy men will be assessed at baseline and at 3 months. They will not participate in a lifestyle intervention. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male, age 18-65 years
- Willing and able to provide informed consent and follow all study procedures, including providing sperm specimens 3 months apart.
- Type 1 or type 2 diabetes diagnosis confirmed by an endocrinologist (for participants in the diabetes groups)
- HbA1c > 7% (for participants in the diabetes groups)
- Overweight (BMI > 25 kg/m2) (for all groups, to ensure groups are similar)
Key exclusion criteria (16 listed)
- Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
- Hepatic disease, including serum alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;
- Severe diabetic retinopathy;
- Congestive heart failure, New York Heart Association (NYHA) class II, III or IV;
- History of myocardial infarction, unstable angina or revascularization within the past 6 months;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lifestyle InterventionParticipants will undergo a 12-week multidisciplinary program for weight control and intensive diabetes management. The program includes adjustments to diabetes medications to enhance weight reduction and improve glycemia, dietary modification, and activity instructions. | Other | Lifestyle Intervention |
| No InterventionParticipants will not undergo an intervention. | Other | Healthy Controls, No-Intervention Controls |
Primary outcome
Spermatozoa concentration
Time frame: 1 year
Sperm will be assessed for concentration, reported as total yield (millions per ml)
2 secondary outcomes
Sperm DNA methylation, reported as genomic location of regions with methylation altered in response to intervention
Time frame: 1 year
RNA Sequencing
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Background: PubMed 28273478Sales VM, Ferguson-Smith AC, Patti ME. Epigenetic Mechanisms of Transmission of Metabolic Disease across Generations. Cell Metab. 2017 Mar 7;25(3):559-571. doi: 10.1016/j.cmet.2017.02.016.
- Derived from this study: PubMed 40108650Su L, Dreyfuss JM, Ferraz Bannitz R, Wolfs D, Hansbury G, Richardson L, Charmant C, Patel J, Ginsburg ES, Racowsky C, Fore R, Efthymiou V, Desmond J, Goldfine A, Ferguson-Smith A, Pan H, Hivert MF, Isganaitis E, Patti ME. Type 2 diabetes impacts DNA methylation in human sperm. Clin Epigenetics. 2025 Mar 20;17(1):49. doi: 10.1186/s13148-025-01853-9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lifestyle Intervention in people with Overweight and Type 2 Diabetes Mellitus, run by Joslin Diabetes Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Spermatozoa concentration (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03860558, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.